Significance
Heart failure is the terminal stage of cardiac hypertrophy, which imposes an enormous clinical and economic burden worldwide. Despite our knowledge on the pathophysiology of the disease, current therapeutic approaches are still largely limited. Cardiac hypertrophy can be regulated at post-translational modifications (PTMs), and several PTMs have been reported in cardiac hypertrrophy and heart failure. In our study, we first reported a novel PTMs, lysine malonylation, in cardiac hypertophy. we found a reduced lysine malonylation in hypertrophic mice hearts in vivo and H9C2 cardiomyocytes after stimulating with angiotensinII for 48 h in vitro. Using affinity purification and LC-MS/MS, we identified 679 malonylated sites in 330 proteins in the hearts of sham and TAC mice. Compared to the sham group, 5 sites in 2 proteins were quantified as downregulated targets using a 2-fold threshold (downregulation <0.5-fold, P < 0.05). Functional analysis showed a significant enrichment in cardiac structure and contraction, cGMP-PKG pathway and metabolism. Notably, we identified a decreased Kmal level in isocitrate dehydrogenase 2 (IDH2), but the protein level of IDH2 has no changed in cardiac hypertrophy, These results highlight that lysine malonylation is associated with cardiac hypertrophy, and may be a new therapeutic target of the disease.